Funds are requested for upgrade of a multinuclear GE 9.4 T/8.9 cm imaging/spectrometer system. This is an eight year old second hand instrument purchased from Stanford University. The instrument is old. there has been a great deal of down time, and the manufacturer has sold its business to Bruker, which will stop supporting this instrument beyond August of 1999. The upgraded system will be employed for the study of isolated cells. tissues. and rodents in vivo. This instrument will be equipped for NMR microscopy, broadline NMR spectroscopy of quadrupolar nuclei (e.g., 23Na, 17(O) and for 1H magic-angle spinning (MAS) and cross polarization experiments of biopsy specimens. Multinuclear MRI and MRS capabilities will be available for in vivo studies of mice and in vitro studies of isolated perfused cells, multicellular spheroids. and organs. In vitro capabilities will include diffusion spectroscopy to distinguish intracellular and extracellular metabolites. Capabilities for performing high resolution multidimensional multinuclear MRS of tissue extracts will be included. A major focus of this program is the study of rodent models of mucopolysaccharide storage diseases, cystic fibrosis, cancer, and multiple sclerosis. Many of the disease models are transgenic mice, and development of MR methods to noninvasively monitor gene therapy is a key objective. Other user projects include studies of the structure and physical properties of cartilage and trabecular bone, of the glucose sensory mechanism and energy metabolism of pancreatic beta-cells. Isotope labeling methods for measuring flux through various metabolic pathways and oxygen consumption rates will be developed. This spectrometer will be housed in the Department of Radiology of the University of Pennsylvania (Penn) School of Medicine. Principal users at Penn include members of the Departments of Radiology, Genetics, Biochemistry & Biophysics. and Radiation Oncology at the School of Medicine, the Departments of Neurology and Radiology at the School of Veterinary Medicine, as well as members of the Institute of Gene Therapy, the Comprehensive Cancer Center and the Diabetes Center. One project from the Thomas Jefferson University Bodine Cancer Center and one from the Childrens' Hospital of Philadelphia are included in this proposal. The instrument will also be available to users from Temple University and the Fox Chase Cancer Center. Institutional commitments include purchase of the original instrument and renovation of space for the spectrometer.